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The Fascinating Role Of Cannabinoids In The Placebo Effect

High on the list of unsolved scientific mysteries is the placebo effect, which causes people to inexplicably recover from illnesses despite receiving a mere sugar pill instead of actual medication. If researchers can get to grips with this intriguing phenomenon and learn to trigger it, then pharmaceutical companies may one day be able to stop producing all their chemical concoctions and start manufacturing nothing but sucrose tablets, saving themselves billions in the process.

For this reason, numerous studies have been conducted with the aim of understanding how the placebo effect works, and evidence is beginning to point towards the cannabinoid system as one of its primary mediators.

Cannabinoids And The Placebo Effect – What’s The Link?

First off, it’s important to understand what the placebo effect actually refers to. Paradoxically, the effect in question is not caused by the placebo itself – otherwise it wouldn’t be a placebo. Rather, it’s the patient’s belief in the efficacy of the placebo, and expectation to heal, that somehow produces a genuine biological response.

For this reason, some scientists argue that the term ‘placebo effect’ should be scrapped and replaced with ‘meaning response’. Whatever you want to call it, though, studies have shown that the mind’s ability to heal the body involves a number of neurological systems that influence inflammation, pain perception and mood – three things which are also highly affected by cannabis.

For instance, the placebo effect has been found to be partially induced by signalling within the brain’s reward circuitry, causing feelings of positivity and enhanced mood. Interestingly, some of these pathways are loaded with cannabinoid receptors, and are therefore activated by the body’s own cannabinoids – or endocannabinoids – in order to produce feelings of euphoria.

Similarly, phytocannabinoids like tetrahydrocannabinol (THC) can bind to these receptors and generate positive feelings, while simultaneously reducing pain sensitivity and suppressing inflammation. Because of this, some scholars have suggested that cannabinoids may indeed be the key to the mind’s ability to heal the body.

Which Cannabinoids Are Involved In the Placebo Effect?

The cannabinoid 1 (CB1) receptor is thought to play a crucial role in the placebo effect, at least in terms of reducing pain. While much more research is needed in order to confirm this, one important study found that inhibiting these receptors virtually eliminates the placebo phenomenon[i].

To conduct the study, researchers gave a non-opioid painkiller to several patients, all of whom responded well to the medication and experienced a reduction in pain. When the scientists then gave these same patients a placebo but told them it was their regular medication, many continued to benefit from a similar decrease in pain, as their belief in the efficacy of the pills triggered a healing response.

When these patients were given a chemical that inhibits CB1 receptors, however, this placebo effect vanished and their pain did not decrease, suggesting that CB1 activity is necessary for the mind to heal the body in the absence of genuine medication.

It is also known that people with naturally higher levels of endocannabinoids are more likely to respond to painkillers, including placebos. This is largely due to an endocannabinoid called anandamide, which is also known as the “bliss molecule” thanks to its ability to generate feelings of joy and wellness.

In the brain, anandamide is broken down by fatty acid amide hydrolase (FAAH), yet roughly half of all people carry a gene that limits their ability to produce FAAH. This reduces their capacity to break down anandamide, which means the cannabinoid tends to accumulate in their brains, triggering positive changes in mood and pain sensitivity. Perhaps unsurprisingly, therefore, studies have shown that people with this gene tend to be much responsive to placebo painkillers[ii].

What About Plant Cannabinoids?

No research has been conducted into whether or not phytocannabinoids like THC and cannabidiol (CBD) have an impact on a person’s ability to experience the placebo effect. However, given that many of the cannabinoids present in cannabis interact with the same receptors as the body’s own endocannabinoids, it’s certainly worth asking a few questions regarding how these compounds may be linked to the healing power of the mind.

In any case, the increasingly apparent involvement of cannabinoids in the placebo effect does at least shed some light on why cannabis is so effective at treating such a broad range of conditions.

[i] Benedetti F, Amanzio M, Rosato R, Blanchard C. Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors. Nature medicine. 2011 Oct;17(10):1228-30. – https://www.nature.com/articles/nm.2435

[ii] Pecina M, Martinez-Jauand M, Hodgkinson C, Stohler CS, Goldman D, Zubieta JK. FAAH selectively influences placebo effects. Molecular psychiatry. 2014 Mar;19(3):385-91. – https://www.nature.com/articles/mp2013124/

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This post is also available in: French

Ben Taub